As a technique for treating tissues and organs damaged by various kinds of diseases, a method of injecting self-renewable and differentiable cells to the tissues and organs to be renewed is receiving attention. A representative example of the cells may be mesenchymal stem cells (MSCs).
The MSCs are multipotent stem cells, which can be differentiated into various kinds of cells. Since the MSCs may be differentiated into various cells and tissues constituting a human body such as osteoblasts, chondrocytes, adipocytes, neuronal cells, epithelial cells, muscles, etc., they are in the limelight as the most critical cells in terms of practice of regenerative medicine. However, to obtain a satisfactory therapeutic effect, it is important the MSCs injected to a tissue are suitably differentiated, and engrafted to a corresponding tissue.
Adipocytes originate from mesoderm-originating stem cells, which can be differentiated into osteoblasts, as well as the adipocytes. According to various studies, it was shown that there is a contrary relationship between differentiations of bone marrow-derived stem cells into adipocytes and osteoblasts (Dorheim M A, et al., J Cell Physiol 1993; 154:317-28.; Beresford J N, et al., J Cell Sci 1992; 102:341-51.). That is, as the differentiation into adipocytes is inhibited, osteogenesis can be increased. It was shown that many transcription factors and intracellular and extracellular signal transduction pathways are closely associated and regulated in the process of differentiating stem cells into adipocytes and osteoblasts. Among the transcription factors, a peroxisome proliferator-activated receptor γ (PPARγ) serves to increase the differentiation into adipocytes, but decrease the differentiation into osteoblasts (Schwartz A V, et al., J Clin Endocrinol Metab 2006; 91:3349-54.; Gimble J M, et al., Mol Pharmacol 1996; 50:1087-94.).
Meanwhile, cryptotanshinone, which is a fat-soluble diterpene-based compound extracted from a dried root of Salvia militorrhiza Bunge, was known to have a pharmacological action of declining an appetite. In an animal test with respect to obese rats, the decline in an appetite and 30% loss of a weight were observed after administration of the cryptotanshinone. However, there were no reports that the cryptotanshinone stimulates the differentiation of stem cells into osteoblasts.